TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21901	65926;65927;65928	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
N2AB	20260	61003;61004;61005	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
N2A	19333	58222;58223;58224	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
N2B	12836	38731;38732;38733	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
Novex-1	12961	39106;39107;39108	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
Novex-2	13028	39307;39308;39309	chr2:178583102;178583101;178583100	chr2:179447829;179447828;179447827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-125
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.4125
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
G/D	None	None	0.001	N	0.257	0.13	0.0762999501168	gnomAD-4.0.0	6.85271E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.6597E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
G/A	0.2309	likely_benign	0.1899	benign	-0.306	Destabilizing	0.124	N	0.418	neutral	N	0.478962427	None	None	N
G/C	0.3279	likely_benign	0.2416	benign	-0.913	Destabilizing	0.883	D	0.617	neutral	D	0.522274508	None	None	N
G/D	0.1619	likely_benign	0.1427	benign	-0.718	Destabilizing	0.001	N	0.257	neutral	N	0.475186598	None	None	N
G/E	0.2473	likely_benign	0.2157	benign	-0.892	Destabilizing	0.157	N	0.438	neutral	None	None	None	None	N
G/F	0.7581	likely_pathogenic	0.6492	pathogenic	-1.088	Destabilizing	0.726	D	0.595	neutral	None	None	None	None	N
G/H	0.4187	ambiguous	0.3421	ambiguous	-0.488	Destabilizing	0.968	D	0.5	neutral	None	None	None	None	N
G/I	0.5194	ambiguous	0.4134	ambiguous	-0.518	Destabilizing	0.396	N	0.588	neutral	None	None	None	None	N
G/K	0.421	ambiguous	0.3756	ambiguous	-0.819	Destabilizing	0.567	D	0.452	neutral	None	None	None	None	N
G/L	0.6434	likely_pathogenic	0.5483	ambiguous	-0.518	Destabilizing	0.396	N	0.564	neutral	None	None	None	None	N
G/M	0.6062	likely_pathogenic	0.5123	ambiguous	-0.512	Destabilizing	0.909	D	0.604	neutral	None	None	None	None	N
G/N	0.1717	likely_benign	0.1563	benign	-0.485	Destabilizing	0.396	N	0.391	neutral	None	None	None	None	N
G/P	0.9401	likely_pathogenic	0.9113	pathogenic	-0.417	Destabilizing	0.726	D	0.498	neutral	None	None	None	None	N
G/Q	0.312	likely_benign	0.2682	benign	-0.8	Destabilizing	0.567	D	0.493	neutral	None	None	None	None	N
G/R	0.3436	ambiguous	0.2914	benign	-0.329	Destabilizing	0.497	N	0.493	neutral	N	0.483152709	None	None	N
G/S	0.1082	likely_benign	0.0961	benign	-0.598	Destabilizing	0.009	N	0.257	neutral	N	0.472174798	None	None	N
G/T	0.2384	likely_benign	0.2011	benign	-0.709	Destabilizing	0.001	N	0.285	neutral	None	None	None	None	N
G/V	0.4155	ambiguous	0.3297	benign	-0.417	Destabilizing	0.331	N	0.558	neutral	D	0.522274508	None	None	N
G/W	0.6301	likely_pathogenic	0.5223	ambiguous	-1.209	Destabilizing	0.968	D	0.572	neutral	None	None	None	None	N
G/Y	0.6108	likely_pathogenic	0.4884	ambiguous	-0.881	Destabilizing	0.909	D	0.591	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.